Expression of C-KIT, CD24, CD44s, and COX2 in benign and non-invasive apocrine lesions of the breast

Virchows Arch. 2016 Sep;469(3):285-95. doi: 10.1007/s00428-016-1966-1. Epub 2016 Jun 10.


Benign apocrine metaplasia (AM) of the adult breast is a very common, but enigmatic lesion. It has been speculated that AM might be a precursor of malignancy or an indicator of a susceptibility of the breast tissue to develop neoplasia, mainly based on comparing the frequency of AM in breast cancer and non-breast cancer patients [1]. Studies using comparative genomic hybridization have supported this by showing similar molecular alterations in benign and malignant apocrine lesions [2]. Few studies, however, have compared expression of biomarkers involved in tumor progression in AM and progressively more advanced atypical apocrine lesions. The expression of C-KIT, COX2, CD24, and CD44s was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded material of 9 AM, 20 apocrine ductal intraepithelial neoplasia (DIN1c-3) and 40 atypical apocrine lesions (not qualifying for DIN1c-3) and compared to expression of the same biomarkers in adjacent normal ductal epithelium. Of the 66 apocrine lesions, 62 (94 %) did not express C-KIT compared to 4/63 (6 %) of the normal glands (Fisher's exact, p < 0.001). COX2 was expressed in a significantly higher proportion of apocrine lesions than of normal glands (49 vs. 14 %, p < 0.001), and the number of apocrine lesions positive for CD24 was found to be higher with increasing aggressiveness of the lesions (Spearman, p < 0.001). In conclusion, benign and non-invasive proliferative apocrine lesions of the breast display immuno-phenotypical characteristics previously ascribed mainly to malignant transformation. This could lend support to the theory that AM is an early step towards malignant transformation, albeit associated with slow progression to carcinoma.

Keywords: Apocrine metaplasia; Breast; C-KIT; CD24; CD44s.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Breast / pathology
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • CD24 Antigen / metabolism
  • Comparative Genomic Hybridization / methods
  • Cyclooxygenase 2 / metabolism*
  • Epithelial Cells / pathology
  • Epithelium / metabolism
  • Epithelium / pathology
  • Female
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Immunohistochemistry / methods
  • Metaplasia / diagnosis
  • Metaplasia / pathology*
  • Middle Aged
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Young Adult


  • Biomarkers, Tumor
  • CD24 Antigen
  • CD24 protein, human
  • CD44S antigen
  • Hyaluronan Receptors
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Proto-Oncogene Proteins c-kit